Research Evaluating an Investigational Medication for Erectile Dysfunction - Post-Prostatectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Research Evaluating an Investigational Medication for Erectile Dysfunction - Post-Prostatectomy (NCT00895011), a randomized phase 3 study. The primary outcome is Change in Percentage of Sexual Attempts in Which Subjects Are Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of avanafil for erectile dysfunction following bilateral nerve-sparing radical prostatectomy. The registry record lists 298 participants enrolled and a completed study. The recorded start was 2009-04, and primary completion was 2011-04.

Participants were assigned to placebo, avanafil 100 mg, or avanafil 200 mg. The primary outcome results are reported for the Intent-to-Treat population, with 96.0 participants analyzed in the placebo group, 94.0 in the 100 mg group, and 96.0 in the 200 mg group. These are the analysis counts for this outcome, not a description of all participants’ later follow-up or availability of measurements.

The primary endpoint was a continuous measure: change from baseline to Week 12 in the percentage of sexual attempts with an erection that lasted long enough for successful intercourse. The registry record reports least-squares means and standard errors for the groups. It also posts comparisons of each dose with placebo. These comparisons are simple unadjusted recalculations from the posted summary statistics; the discrepancy flag is false.

The record does not report the trial’s original sample-size justification, detailed randomization procedures, specific blinding procedures, or the statistical model used for the least-squares means. The registry record also does not report the investigators’ full statistical analysis plan. Those details cannot be inferred from the study’s randomized and double-blind design labels.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Subjects meeting the initial eligibility criteria completed a 4-week non-treatment run-in period during which information on each attempt at intercourse was recorded. At the end of the run-in, subjects meeting the randomization criteria were eligible for assignment to one of the treatment groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Number of participants analyzed represents the Intent-to-Treat population.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Percentage of Sexual Attempts in Which Subjects Are Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse, measured over Baseline, Week 12.

The primary endpoint measures change from baseline to Week 12 in the percentage of sexual attempts for which participants reported that their erection lasted long enough for successful intercourse. The registry record says the measure came from “yes” responses to Sexual Encounter Profile diary question 3: “Did your erection last long enough for you to have successful intercourse?” The unit is percentage of sexual attempts.

This endpoint captures a participant-reported outcome tied to a specific aspect of sexual activity. It is not a measure of all erectile function or of every aspect of sexual experience. Because it is expressed as a percentage of attempts, a change describes movement in that measure over time, rather than a change in the number of participants or a relative percentage change.

The registry reports least-squares mean change for each group. In general, a least-squares mean is a model-based group mean; the registry record does not report enough detail to identify the model or any covariates used. The reported values are 13.9 for placebo, 28.0 for avanafil 100 mg, and 29.4 for avanafil 200 mg. They describe average change in the endpoint for the analyzed groups, not the experience of every participant. The record does not report the distribution of individual changes or the proportion of participants who improved.

7. Results Posted in the Registry

• Avanafil 100 mg: mean 28.00 versus 13.90 on control; difference 14.10 (95% CI 4.45 to 23.75), standardized effect d = 0.42; z-test p = 0.004.
• Avanafil 200 mg: mean 29.40 versus 13.90 on control; difference 15.50 (95% CI 6.14 to 24.86), standardized effect d = 0.47; z-test p = 0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The study design is described as randomized, double-blind, placebo-controlled, and parallel-group. In general, random assignment is intended to make treatment groups comparable on average, while blinding is intended to reduce the influence of knowledge of assignment on participant experience, care, or outcome assessment. These are general purposes of the design features; the registry record does not report the specific randomization or blinding procedures used. A parallel-group design assigns participants to a group for comparison rather than describing a within-person crossover between treatments.

What does a least-squares mean represent?

The primary outcome is continuous: it records a percentage measure and its change over time. The registry reports least-squares mean changes of 13.9 for placebo, 28.0 for avanafil 100 mg, and 29.4 for avanafil 200 mg. In general, a least-squares mean is an estimated mean from a statistical model, potentially adjusted for factors included in that model. The record does not identify the model, its covariates, or the estimation method beyond naming the least-squares mean. It is therefore not possible to say which adjustments, if any, contributed to these values.

The reported standard errors are 3.42 for placebo, 3.54 for avanafil 100 mg, and 3.33 for avanafil 200 mg. In general, a standard error describes the sampling uncertainty of an estimated mean: it reflects how much the estimate would vary across repeated samples under the assumptions of the analysis. It is not the spread of individual participants’ outcomes. A standard deviation, by contrast, describes variation among individual observations. The registry reports standard errors for the primary group means, not standard deviations for participant-level outcomes.

How should the group comparisons be understood?

The posted comparisons estimate the mean difference between each avanafil dose and placebo. For avanafil 100 mg, the reported difference is 14.1, with an interval from 4.453 to 23.75 and unadjusted p = 0.004. For avanafil 200 mg, it is 15.5, with an interval from 6.144 to 24.86 and unadjusted p = 0.001. The comparison estimates are simple unadjusted recalculations from the posted summary statistics. The discrepancy flag is false, so there is no recorded discrepancy requiring a different interpretation of these recalculated values.

In general, a mean difference expresses the separation between group averages on the endpoint’s scale. A confidence interval describes uncertainty in that estimated difference, subject to the method and assumptions used. A p-value measures how unusual the observed data, or more extreme data, would be under a specified null model. It does not give the probability that the null hypothesis is true, and it does not measure the size or importance of the effect. The registry record does not report the confidence level for the posted intervals or the full testing procedure behind the original trial analysis.

Why can over-dispersion matter?

General note: for count outcomes, over-dispersion occurs when variability is greater than a model expects. It can make standard errors too small if the model does not account for the extra variability. That issue is not the central feature of this primary endpoint, which is reported as a continuous measure. The registry record does not report an over-dispersion analysis for this outcome.

What is not documented about the analysis?

The record identifies the Intent-to-Treat population for the primary outcome and gives analysis counts by group. It does not explain how that population was defined in practice, how missing diary data were handled, or whether any participants were excluded from particular analyses. The model used for the least-squares means, any covariate adjustment, and the original trial’s multiplicity procedure are not reported in the registry record. Interim analyses and the trial’s original statistical analysis plan are not reported in the registry record either. These details should not be inferred from the presence of group estimates, standard errors, intervals, or p-values.

10. Confidence Intervals and Precision

The estimated unadjusted mean difference for avanafil 100 mg versus placebo is 14.1, with an interval from 4.453 to 23.75. For avanafil 200 mg versus placebo, the estimated difference is 15.5, with an interval from 6.144 to 24.86. These intervals convey uncertainty about the estimated average differences: values across each interval are compatible with the posted summary data under the calculation’s assumptions. The registry record does not report the confidence level for the intervals.

Neither interval is a point estimate of the true difference. The point estimates, 14.1 and 15.5, are the central reported estimates; the interval endpoints show that plausible values are spread around them. In general, narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. Precision depends on factors including variability, sample information, and the analysis method. The registry record reports group standard errors but does not document the full model or interval calculation method.

The standard errors for the group means are 3.42 for placebo, 3.54 for avanafil 100 mg, and 3.33 for avanafil 200 mg. These describe uncertainty in estimated group means, not individual-level variability. The posted group analysis counts are 96.0, 94.0, and 96.0, respectively. Those counts and the standard errors help characterize the reported estimates, but they do not establish that all missingness or other sources of uncertainty have been accounted for.

The intervals and unadjusted p-values summarize the posted comparisons, not the results of an adjustment for multiple testing or missing data. The registry record does not report whether such adjustments were part of the original analysis.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for each two-group comparison, not total events. They are planning illustrations computed from the observed effect, not the trial’s original design assumptions. The original sample-size justification and design assumptions are not reported in the registry record.

The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect as the effect to detect. The rows for planning for 100% of the observed effect use the full observed estimate; rows for planning for 75% or 50% use progressively smaller effects. In general, smaller effects are harder to distinguish from random variation, so they require more participants for the same target power under the stated assumptions.

For the avanafil 100 mg comparison, planning for 100% of the observed effect gives 91 participants per arm for 80% power and 122 participants per arm for 90% power. Planning for 75% gives 162 participants per arm for 80% power and 217 participants per arm for 90% power. Planning for 50% gives 364 participants per arm for 80% power and 487 participants per arm for 90% power.

For avanafil 200 mg, planning for 100% gives 72 participants per arm for 80% power and 96 participants per arm for 90% power. Planning for 75% gives 128 participants per arm for 80% power and 171 participants per arm for 90% power. Planning for 50% gives 286 participants per arm for 80% power and 383 participants per arm for 90% power.

In general, 80% or 90% power describes the chance of detecting an effect of the specified size under the planning assumptions if that effect is present. These figures are not observed power; they are sample-size planning illustrations based on the observed estimates.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 14.100; pooled standard deviation σ = 33.913.
2. n = 2 × (1.96 + 0.842)² × 33.913² / 14.100² = 90.8, rounded up to 91 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 14.1                      # observed difference in means
sigma <- 33.9134078173697                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(895011)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 91 (80% power), 122 (90% power)
 75% of observed effect: n per arm = 162 (80% power), 217 (90% power)
 50% of observed effect: n per arm = 364 (80% power), 487 (90% power)
power.t.test: 91.8 
Simulated power at n = 91 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The primary outcome results include two comparisons with placebo: one for avanafil 100 mg and one for avanafil 200 mg. When multiple hypotheses are tested, the chance of at least one false-positive finding can increase. In general, a multiplicity procedure can address that issue by adjusting the testing threshold or reported inference. The registry record does not report whether the original analysis used a multiplicity adjustment, how any adjustment was performed, or which comparisons were designated for confirmatory testing. The posted p-values are unadjusted recalculations and should be read as such.

The registry record identifies the primary outcome population as the Intent-to-Treat population and gives analysis counts of 96.0 for placebo, 94.0 for avanafil 100 mg, and 96.0 for avanafil 200 mg. It does not describe how the Intent-to-Treat population was operationalized, whether all randomized participants contributed to the endpoint analysis, or how participants with unavailable outcome data were handled. Missing-data methods, imputation procedures, and sensitivity analyses are not reported in the registry record.

The record lists three outcome measures and no posted secondary outcome results. It lists no analysis records. This does not provide the details needed to reconstruct the full statistical analysis or determine whether other outcomes or analyses were considered by investigators. The original protocol and statistical analysis plan are not reported in the registry record. Interim analyses are not reported in the registry record.

These omissions matter because the treatment-effect estimates, their uncertainty, and the interpretation of p-values can depend on decisions about missing observations, model specification, and multiple testing. The posted results still allow a description of the reported group means and the simple unadjusted comparisons, but they do not establish how those choices were addressed in the trial’s own full analysis.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures report zero affected participants in each group: 0 of 100 at risk for placebo, 0 of 99 at risk for avanafil 100 mg, and 0 of 99 at risk for avanafil 200 mg. These are group-specific counts of participants affected, not counts of all events. The registry record lists no serious adverse event terms.

For other adverse events, the record reports 1 of 100 participants affected in the placebo group, 16 of 99 in the avanafil 100 mg group, and 27 of 99 in the avanafil 200 mg group. These figures are separate from the serious adverse event counts. They describe affected participants in the recorded risk populations; the record does not provide event-level detail in these figures.

Deaths are not reported in the registry record. The safety figures are descriptive and should be read with their group-specific risk counts and the record’s limits. They do not by themselves describe event timing, severity beyond the serious-event category, duration, or causal attribution.

15. What the Result Does, and Does Not, Mean

The posted results describe average change in a specific participant-reported measure between baseline and Week 12. Mean changes were 13.9 for placebo, 28.0 for avanafil 100 mg, and 29.4 for avanafil 200 mg. The unadjusted recalculated mean differences versus placebo were 14.1 for avanafil 100 mg and 15.5 for avanafil 200 mg. Their respective intervals were 4.453 to 23.75 and 6.144 to 24.86.

These findings do not establish the experience of every participant. Group averages can conceal variation in individual responses, and the registry record does not report the distribution of individual changes or the proportion of participants meeting a particular improvement threshold. Nor do the results describe outcomes beyond Week 12 or outcomes not included in the posted primary measure.

The comparison estimates are unadjusted recalculations from posted summary statistics. The registry record does not report the confidence level for the intervals, the full model specification, the original multiplicity approach, or the handling of missing endpoint data. These gaps limit how completely the original statistical analysis can be reconstructed. The record also does not post secondary outcome results, so the primary endpoint should not be treated as a summary of all outcomes assessed in the study.

The figures do not show a direct comparison between avanafil 100 mg and avanafil 200 mg. Both comparisons use placebo as the reference, so their estimates cannot establish whether the doses differ from each other. The safety counts are a separate descriptive component and do not substitute for a comprehensive safety analysis.

In general, statistical estimates describe evidence within the study’s population, measurement, and follow-up. They do not alone determine the relevance of the measure to an individual or establish effects in populations or settings not described in the registry record. These results are a statistical description of the posted trial record, not medical advice.

16. Why This Trial Matters Statistically

This trial is statistically informative because it reports a continuous, participant-reported primary outcome for three randomized groups and provides group least-squares mean changes, standard errors, and comparisons with placebo. That allows readers to distinguish the group-level changes from the estimated differences between groups, and to consider uncertainty rather than relying only on a single estimate.

The two active-dose comparisons are useful to examine separately, while recognizing that the record does not report a direct comparison between doses. The observed estimates are 14.1 for avanafil 100 mg versus placebo and 15.5 for avanafil 200 mg versus placebo. Their intervals and unadjusted p-values help describe the uncertainty and evidence associated with each comparison, but do not provide the missing detail about multiplicity or the trial’s original analysis plan.

The record also illustrates why the analysis population and outcome definition matter. The endpoint is based on diary responses about whether an erection lasted long enough for successful intercourse, and the primary analysis is identified as Intent-to-Treat. The record supplies group analysis counts but does not explain missing-data handling or the exact statistical model. Those details are important to interpreting model-based means and comparisons.

Finally, the sample-size planning illustrations show how required group sizes change when the assumed effect is reduced from the observed effect. They are not a reconstruction of the trial’s design decision. Keeping planned sample size, observed group estimates, and inferential uncertainty conceptually separate is essential when reading registry results.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The record gives the study’s broad design labels but does not report detailed procedures for randomization, concealment, or blinding. It does not report the full statistical analysis plan, the model behind the least-squares means, or any covariate adjustments. These omissions restrict independent reconstruction of the original analysis.

The primary outcome analysis counts are reported, but the record does not explain how missing diary responses were handled, whether participants with incomplete data contributed to the analysis, or whether sensitivity analyses were conducted. The meaning of the stated Intent-to-Treat population therefore cannot be assessed beyond the label and reported counts.

The comparison intervals are posted without a stated confidence level. The comparisons are simple unadjusted recalculations from the posted summary statistics, and the registry record does not report whether the original trial analysis adjusted for multiple comparisons. No direct comparison between the avanafil doses is reported. Secondary outcome results are not posted, and the record lists no analysis records.

The primary endpoint concerns one diary-based measure at Week 12. The registry record does not provide individual-level outcome distributions or longer-term primary endpoint results. The safety record provides affected-participant counts, but deaths are not reported in the registry record and serious adverse event terms are not listed. These limits mean that the registry results do not give a complete account of all outcomes, analysis decisions, or safety details from the study.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Research Evaluating an Investigational Medication for Erectile Dysfunction - Post-Prostatectomy — NCT00895011.
• Registry record last updated 2012-10-01; status last verified 2012-09.
• Results first posted 2012-06-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry record describes a completed, randomized, double-blind, placebo-controlled, parallel-group, multicenter phase 3 study of avanafil for erectile dysfunction following bilateral nerve-sparing radical prostatectomy. It reports enrollment of 298, a start date of 2009-04, and primary completion in 2011-04.

The primary outcome was change from baseline to Week 12 in the percentage of sexual attempts with an erection lasting long enough for successful intercourse. The record reports least-squares mean changes of 13.9 for placebo, 28.0 for avanafil 100 mg, and 29.4 for avanafil 200 mg. Unadjusted recalculated mean differences versus placebo were 14.1 and 15.5, respectively.

The record also reports serious and other adverse-event counts by group. It does not report secondary outcome results, the original sample-size justification, detailed missing-data methods, the confidence level for comparison intervals, or the full statistical analysis plan.